PROTECTIVE EFFECT OF SHINGLES VACCINE ON ALZHEIMER’S DISEASE CAN BE MODULATED BY RISK VARIANT OF NECTIN2 GENE

Abstract The aging-related decline in immune surveillance was suggested to play a major role in Alzheimer’s disease (AD). Adult vaccinations may support the aging immune system beyond prevention of the target disease, and through this provide a protection against AD. Such off-target effects of vaccines may potentially be affected by genetic risk factors for AD. To explore this possibility, we estimated association of the vaccination against shingles (reactivated herpes zoster virus infection) received between ages 65-75 with AD onset at ages 75+ in the Health and Retirement Study (HRS) survey participants, comparing the carriers and non-carriers of rs6859 A allele of NECTIN2 gene (AD risk factor that is also involved in vulnerability to viral infections). We used logistic regression model with covariates including sex, race, education, and smoking status. We found that shingles vaccine was significantly associated with lower odds of AD onset later in life, in the total sample (p-value=0.021; OR=0.55 (0.33, 0.92)). After stratification by genotype, the protective effect of vaccine became stronger in rs6859 A carriers (p-value=0.016; OR=0.44 (0.22, 0.86)), but disappeared in the non-carriers, for both significance and size (p-value=0.81; OR=0.90). We conclude that adult shingles vaccine may reduce chances of AD at older ages, and this effect appears more beneficial for carriers of rs6859 A allele of NECTIN2 gene. Repurposing of existing vaccines may benefit the aging immune system, and be a promising approach to personalized genotype-tailored prevention of AD.

Arkasnas, Fayetteville, Arkansas, United States,5. Neurotrack,Redwood City,California,United States Alzheimer's disease (AD) is the 7th leading cause of death and 6th most burdensome disease among US older adults.With pharmacological treatments for AD being predominantly ill-effective, alternative, non-pharmacological prevention and treatment strategies warrant exploration.Personal health coaching provides individualized strategies designed to improve physical, social, and emotional health leading to positive behavior changes that may improve cognitive ability.The purpose of the present investigation was to examine the effects of a Health Coaching (HC) intervention on cognitive outcomes.Adults (n=182) over 45 years of age were randomly assigned to HC or control arm of a 12-month intervention.Participants (age = 61.9+ 8.4 years) had their cognition (ECog-12) tested at baseline, 16, and 52 weeks.Participants assigned to the HC intervention met with a health coach once per month to establish healthful goals and implementation strategies improving the health and well-being of the participants.The control group received bi-weekly emails including similar information presented during the health coaching sessions.Results revealed a main effect for time for improved ECog-12 scores (p=.04) with a 3.2% improvement in ECog-12 after 52 weeks.Upon further analysis, HC had a significant improvement in cognitive performance after both 16 and 52 weeks, while the control group remained unchanged.Improvement in self-reported cognition was 4.0% (p=.03) and 5.5% (p=.01) in the HC group after 16 and 52 weeks, respectively.These results suggest HC is an effective non-pharmacological prevention strategy for cognitive decline among a group of adults at-risk for developing AD.Given the paucity of dementia treatments, identifying contributors to cognitive decline from midlife is important to delay onset of symptoms.Low physical activity (PA) and nightly sleep duration outside 6-8 hours are key interrelated factors thought to contribute to cognitive decline and dementia; how PA and sleep combine to influence cognitive ageing is not well-explored.We used linear mixed models to examine independent and joint associations of PA (low, high) and sleep duration (short [< 6 hours], optimal [6][7][8], long [>8]) with 10-year cognitive trajectories in cognitively-healthy adults aged ≥50 years from the English Longitudinal Study of Ageing (N=8958).We found low PA (p< 0.001) and suboptimal sleep (p=0.01) were independently associated with worse cognitive performance; short sleep was also associated with faster cognitive decline (p=0.04).At baseline, high PA/optimal sleepers had higher cognitive scores than all sleep categories in the low PA category (e.g.difference high PA/optimal-low PA/short at age 50=0.14 [0.05, 0.24] standard deviations), with no difference in cognitive scores between sleep categories within the high PA category.Differences remained consistent over 10 years of follow-up, except high PA/short sleepers who declined faster than high PA/optimal sleepers, such that scores at 10 years were commensurate with low PA (difference high PA/optimal-high PA/short=0.20 [0.08, 0.33]; high PA/ optimal-low PA/short=0.22 [0.11, 0.34]).Baseline cognitive benefits afforded by high PA were insufficient to ameliorate rapid cognitive decline associated with short sleep.While WHO identify PA as a key target for maintaining cognitive health, PA interventions may be ineffective without considering sleep habits.

PHYSICAL ACTIVITY AND THE DEVELOPMENT OF DEMENTIA BETWEEN AGES 70 AND 95
Irit Stessman-Lande 1 , Jochanan Stessman 2 , and Jeremy Jacobs 1 , 1. Faculty of Medicine, Hebrew University of Jerusalem,and Hadassah Medical Center,Israel,Jerusalem,Yerushalayim,Israel,2. Hebrew University of Jerusalem,and Hadassah Medical Center,Israel,Jerusalem,Yerushalayim,Israel Whilst the protective effects of physical activity (PA) on cognitive function are well documented, it remains unclear if the preventive effect continues irrespective of advancing age.This study examines the association between physical activity and subsequent dementia between ages 70-95.The Jerusalem Longitudinal Study (1990Study ( -2023) ) prospectively follows a representative community-dwelling cohort born 1920-21, assessed at home visit during 1990,1998, 2005, 2010, 2015 at ages 70, 78, 85, 90, and 95 (n=430, 715, 1136, 660, 492) respectively.Comprehensive assessment included Mini Mental State Examination (MMSE) defining dementia (≤23/30), and PA assessment, dichotomized to Active (PA-A) (>4hours a week) versus Sedentary (PA-S) (< 4 hours weekly).Logistic regression analyses determined Odds Ratios (OR) for developing dementia, adjusted for baseline MMSE, gender, education, depression and BADL.At ages 70, 78, 85, 85, 90, and 95 the frequency of PA-A was 45.9%, 69.7%, 48.7%, 9.5%, 11.9%; and frequency of dementia among PA-A vs. PA-S was 1.7% vs. 5.0%, 1.7% vs. 12.6%, 10.6% vs. 48.5%,8.6% vs. 35.5%,18.3% vs. 29.9%(all p< 0.0001 except age 70 due to small numbers) respectively.Adjusted ORs ratios among PA-A at baseline for subsequently developing dementia between ages 78-85, 85-90, 90-95 were: OR 0.44 (95%CI 0.20-0.98);OR 0.52 (95%CI 0.30-0.90);OR 0.37 (95%CI 0.13-1.07)respectively.Our findings show that physical activity is associated with reduced development of dementia throughout follow-up between ages 70-95, and support the hypothesis that there is no upper age-limit to the beneficial effects of PA on cognition.The aging-related decline in immune surveillance was suggested to play a major role in Alzheimer's disease (AD).Adult vaccinations may support the aging immune system beyond prevention of the target disease, and through this provide a protection against AD.Such off-target effects of vaccines may potentially be affected by genetic risk factors for AD.To explore this possibility, we estimated association of the vaccination against shingles (reactivated herpes zoster virus infection) received between ages 65-75 with AD onset at ages 75+ in the Health and Retirement Study (HRS) survey participants, comparing the carriers and non-carriers of rs6859 A allele of NECTIN2 gene (AD risk factor that is also involved in vulnerability to viral infections).We used logistic regression model with covariates including sex, race, education, and smoking status.We found that shingles vaccine was significantly associated with lower odds of AD onset later in life, in the total sample (p-value=0.021;OR=0.55 (0.33, 0.92)).After stratification by genotype, the protective effect of vaccine became stronger in rs6859 A carriers (p-value=0.016;OR=0.44 (0.22, 0.86)), but disappeared in the non-carriers, for both significance and size (p-value=0.81;OR=0.90).We conclude that adult shingles vaccine may reduce chances of AD at older ages, and this effect appears more beneficial for carriers of rs6859 A allele of NECTIN2 gene.Repurposing of existing vaccines may benefit the aging immune system, and be a promising approach to personalized genotypetailored prevention of AD.

HEALTH CARE, PUBLIC HEALTH
Abstract citation ID: igad104.0414

ASSOCIATIONS BETWEEN HEARING LOSS AND HEALTH CARE UTILIZATION: EVIDENCE FROM NHATS Emmanuel Garcia, and Nicholas Reed, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States
We investigated the association between self-reported hearing loss and healthcare utilization among community dwelling older Medicare beneficiaries (age ≥65) who were enrolled in the 2011 cycle of the National Health and Aging Trends Study (NHATS).Participants' survey data were linked to fee-for-service Medicare claims data during the 2011-2016 period.Hearing loss was ascertained using based on participants' hearing aid use, and difficulty hearing in various noisy situations.Those who reported any difficulty hearing or reported hearing aid use were categorized as having hearing loss.Healthcare utilization included: (1) number of inpatient hospitalizations, (2) number of Emergency Department visits, and (3) total number of days spent during hospitalizations per calendar year.Each participant with hearing loss was matched to a participant without hearing loss using a one-to-one propensity score matching to minimize confounding bias.Using generalized estimating equations, we found that among our matched sample those with hearing loss had 21% (Incidence Rate [IR]=1.21;95% Confidence Interval [CI]= 1.06,1.37)higher rates of emergency department visits, and 48% (IR = 1.48; 95% CI: 1.20,1.82)higher number of days spent in a hospital over the 6-year period from 2011-2016.No association was found between hearing loss and the number of hospitalizations.These finding suggest that older adults with hearing loss may be at risk for increased healthcare utilization.Interventions for hearing loss, such as the use of hearing aids, might reduce healthcare utilization and associated expenditures among older adults in the U.S. Medicare program.The number of caregivers across the nation is growing.A three-way collaboration is examining their knowledge and attitudes related to the connection between oral health and overall health.Currently, little is known about caregiver oral health beliefs and how they relate to oral health care for older adult care recipients (CRs).Survey data from the MOTIVATE at Home program from 135 caregivers/care partners (CPs) across rural Maine were analyzed (age: M = 61 years, SD = 13, range= 25 to 85; 85.2% female).Care partners who felt they have a role in preventing tooth decay were more likely to report an oral health visit in the last year for their CR (M = .75,SD = .438;t(84)= -2.66, p=.009).Caregivers whose CR had not had dental care in the last year were less comfortable talking with dental providers (M = 1.50, SD = .632;t(92.84)=-3.01, p = .003),and non-dental health care providers (M = 1.53,SD =.754; t(94.06)= -2.42,p=.017) about oral health.For CRs who do not have a regular dentist, CPs were less comfortable in speaking with the CR about oral health care (M = 1.58,SD = .751;t(42.13)= -2.23;p=.031).These findings are currently informing the development of an educational intervention for CRs which will: Emphasize the importance of regular oral health visits; Improve understanding of the CP role in promoting oral health; Provide tools for conversations with a range of providers.

HOSPICE CLINICIANS' WILLINGNESS TO BE PRESENT DURING MEDICAL AID IN DYING: A CONTENT ANALYSIS OF RATIONALES
Todd Becker 1 , John Cagle 1 , Cindy Cain 2 , Nancy Kusmaul 3 , Joan Davitt 1 , and Paul Sacco 1 , 1. University of Maryland, Baltimore, Baltimore, Maryland, United States, 2. University of Alabama at Birmingham,Birmingham,Alabama,United States,3. University of Maryland Baltimore County,Baltimore,Maryland,United States Although clinician presence during medical aid in dying (MAID) may facilitate relief for patients, federal, state, and organizational policy discourage presence.Given the lack of direct examination, we aimed to describe hospice clinicians' willingness to be present during MAID and categorize their rationales.This cross-sectional analysis used Qualtrics data collected from a convenience sample of 75 hospice clinicians.We recruited participants through hospice and palliative care membership associations for physicians, nurses, social